Common Stereotactic Space Research Articles

An open access resource for functional brain connectivity from fully awake marmosets

The common marmoset (Callithrix jacchus) is quickly gaining traction as a premier neuroscientific model. However, considerable progress is still needed in understanding the functional and structural organization of the marmoset brain to rival that documented in longstanding preclinical model species, like mice, rats, and Old World primates. To accelerate such progress, we present the Marmoset Functional Brain Connectivity Resource (marmosetbrainconnectome.org), currently consisting of over 70 h of resting-state fMRI (RS-fMRI) data acquired at 500 µm isotropic resolution from 31 fully awake marmosets in a common stereotactic space. Three-dimensional functional connectivity (FC) maps for every cortical and subcortical gray matter voxel are stored online. Users can instantaneously view, manipulate, and download any whole-brain functional connectivity (FC) topology (at the subject- or group-level) along with the raw datasets and preprocessing code. Importantly, researchers can use this resource to test hypotheses about FC directly – with no additional analyses required – yielding whole-brain correlations for any gray matter voxel on demand. We demonstrate the resource's utility for presurgical planning and comparison with tracer-based neuronal connectivity as proof of concept. Complementing existing structural connectivity resources for the marmoset brain, the Marmoset Functional Brain Connectivity Resource affords users the distinct advantage of exploring the connectivity of any voxel in the marmoset brain, not limited to injection sites nor constrained by regional atlases. With the entire raw database (RS-fMRI and structural images) and preprocessing code openly available for download and use, we expect this resource to be broadly valuable to test novel hypotheses about the functional organization of the marmoset brain.

Striatal and Thalamic Auditory Response During Deep Brain Stimulation for Essential Tremor: Implications for Psychosis

The P50, a positive auditory-evoked potential occurring 50 msec after an auditory click, has been characterized extensively with electroencephalography (EEG) to detect aberrant auditory electrophysiology in disorders like schizophrenia (SZ) where 61-74% have an auditory gating deficit. The P50 response occurs in primary auditory cortex and several thalamocortical regions. In rodents, the gated P50 response has been identified in the reticular thalamic nucleus (RT)-a deep brain structure traversed during deep brain stimulation (DBS) targeting of the ventral intermediate nucleus (VIM) of the thalamus to treat essential tremor (ET) allowing for interspecies comparison. The goal was to utilize the unique opportunity provided by DBS surgery for ET to map the P50 response in multiple deep brain structures in order to determine the utility of intraoperative P50 detection for facilitating DBS targeting of auditory responsive subterritories. We developed a method to assess P50 response intraoperatively with local field potentials (LFP) using microelectrode recording during routine clinical electrophysiologic mapping for awake DBS surgery in seven ET patients. Recording sites were mapped into a common stereotactic space. Forty significant P50 responses of 155 recordings mapped to the ventral thalamus, RT and CN head/body interface at similar rates of 22.7-26.7%. P50 response exhibited anatomic specificity based on distinct positions of centroids of positive and negative responses within brain regions and the fact that P50 response was not identified in the recordings from either the internal capsule or the dorsal thalamus. Detection of P50 response intraoperatively may guide DBS targeting RT and subterritories within CN head/body interface-DBS targets with the potential to treat psychosis and shown to modulate schizophrenia-like aberrancies in mouse models.

High-Frequency Oscillations in the Normal Human Brain.

High-frequency oscillations (HFOs) are a promising biomarker for the epileptogenic zone. It has not been possible, however, to differentiate physiological from pathological HFOs, and baseline rates of HFO occurrence vary substantially across brain regions. This project establishes region-specific normative values for physiological HFOs and high-frequency activity (HFA). Intracerebral stereo-encephalographic recordings with channels displaying normal physiological activity from nonlesional tissue were selected from 2 tertiary epilepsy centers. Twenty-minute sections from N2/N3 sleep were selected for automatic detection of ripples (80-250Hz), fast ripples (>250Hz), and HFA defined as long-lasting activity > 80Hz. Normative values are provided for 17 brain regions. A total of 1,171 bipolar channels with normal physiological activity from 71 patients were analyzed. The highest rates of ripples were recorded in the occipital cortex, medial and basal temporal region, transverse temporal gyrus and planum temporale, pre- and postcentral gyri, and medial parietal lobe. The mean rate of fast ripples was very low (0.038/min). Only 5% of channels had a rate > 0.2/min HFA was observed in the medial occipital lobe, pre- and postcentral gyri, transverse temporal gyri and planum temporale, and lateral occipital lobe. This multicenter atlas is the first to provide region-specific normative values for physiological HFO rates and HFA in common stereotactic space; rates above these can now be considered pathological. Physiological ripples are frequent in eloquent cortex. In contrast, physiological fast ripples are very rare, making fast ripples a good candidate for defining the epileptogenic zone. Ann Neurol 2018;84:374-385.

Atlas of the normal intracranial electroencephalogram: neurophysiological awake activity in different cortical areas.

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Toward an electrophysiological "sweet spot" for deep brain stimulation in the subthalamic nucleus.

Enhanced beta-band activity recorded in patients suffering from Parkinson's Disease (PD) has been described as a potential physiomarker for disease severity. Beta power is suppressed by Levodopa intake and STN deep brain stimulation (DBS) and correlates with disease severity across patients. The aim of the present study was to explore the promising signature of the physiomarker in the spatial domain. Based on local field potential data acquired from 54 patients undergoing STN-DBS, power values within alpha, beta, low beta, and high beta bands were calculated. Values were projected into common stereotactic space after DBS lead localization. Recorded beta power values were significantly higher at posterior and dorsal lead positions, as well as in active compared with inactive pairs. The peak of activity in the beta band was situated within the sensorimotor functional zone of the nucleus. In contrast, higher alpha activity was found in a more ventromedial region, potentially corresponding to associative or premotor functional zones of the STN. Beta- and alpha-power peaks were then used as seeds in a fiber tracking experiment. Here, the beta-site received more input from primary motor cortex whereas the alpha-site was more strongly connected to premotor and prefrontal areas. The results summarize predominant spatial locations of frequency signatures recorded in STN-DBS patients in a probabilistic fashion. The site of predominant beta-activity may serve as an electrophysiologically determined target for optimal outcome in STN-DBS for PD in the future. Hum Brain Mapp 38:3377-3390, 2017. © 2017 Wiley Periodicals, Inc.

A Diffusion Tensor Imaging Analysis of White Matter Disease in Corticobasal Syndrome (P05.041)

Objective: To determine the regions of white matter (WM) atrophy in corticobasal syndrome (CBS) using different methods of diffusion tensor imaging (DTI) analysis. Background CBS is a clinical syndrome mostly associated with frontotemporal lobar degeneration (FTLD), where gray matter atrophy predominantly encompasses frontal and parietal lobes. Although little is known about the pattern of WM disease in CBS, it is known that tau, the histopathological basis of corticobasal degeneration (CBD), has substantial WM burden. For neurodegenerative diseases, there is no gold standard for MRI-based WM analysis. Here, we compared two user-independent approaches in analyzing WM: tract-specific analysis (TSA) and whole-brain analysis. Both used fractional anisotropy (FA), which is sensitive to the integrity of white matter fiber tracts. Design/Methods: In 11 CBS patients and 35 demographically-matched healthy seniors, we analyzed 30-direction diffusion-weighted images. We extracted FA for each individual subject, and registered the image to a common stereotactic space. For TSA, 11 tracts were segmented from a DTI template, converted to 3D binary structures, and modeled as medial meshes to reflect maximum FA locally. For the whole-brain analysis, images were analyzed in local space, localized to a publicly available probabilistic template (ICDM-DTI-81), and then compared statistically with seniors in SPM8. Results: TSA revealed reduced FA in CBS relative to seniors in right uncinate, arcuate fasciculus, and inferior frontal-occipital fasiculus; and bilateral corpus callosum, corticospinal tract and superior longitudinal fasiculus. Whole-brain analysis also revealed reduced FA relative to seniors in the corpus callosum, corticospinal tract, fornix, inferior longitudinal fasiculus, superior longitudinal fasciculus, inferior frontal-occipital fasiculus, and external capsule. Conclusions: In addition to grey matter atrophy, CBS patients have considerable WM disease. TSA and whole-brain analyses display largely overlapping findings, validating user-independent approaches to DTI analyses of WM disease. Supported by: HD060406, NS44266, NS53488, AG15116, AG17586, AG32953, the Wyncote Foundation, NS065347, DA022807, EB006266, NS045839, EB009321, K25 AG027785. Disclosure: Dr. Chandrasekaren has nothing to disclose. Dr. McMillan has nothing to disclose. Dr. Brun has nothing to disclose. Dr. Cook has nothing to disclose. Dr. Yushkevich has nothing to disclose. Dr. Gee has received research support from Pfizer Inc. Dr. Grossman has nothing to disclose.

The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study

Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon is accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we used an event-related design, which allowed us to isolate trial-related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial-related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries.

An image-driven parameter estimation problem for a reaction-diffusion glioma growth model with mass effects.

We present a framework for modeling gliomas growth and their mechanical impact on the surrounding brain tissue (the so-called, mass-effect). We employ an Eulerian continuum approach that results in a strongly coupled system of nonlinear Partial Differential Equations (PDEs): a reaction-diffusion model for the tumor growth and a piecewise linearly elastic material for the background tissue. To estimate unknown model parameters and enable patient-specific simulations we formulate and solve a PDE-constrained optimization problem. Our two main goals are the following: (1) to improve the deformable registration from images of brain tumor patients to a common stereotactic space, thereby assisting in the construction of statistical anatomical atlases; and (2) to develop predictive capabilities for glioma growth, after the model parameters are estimated for a given patient. To our knowledge, this is the first attempt in the literature to introduce an adjoint-based, PDE-constrained optimization formulation in the context of image-driven modeling spatio-temporal tumor evolution. In this paper, we present the formulation, and the solution method and we conduct 1D numerical experiments for preliminary evaluation of the overall formulation/methodology.

Automatic curvilinear reformatting of three-dimensional MRI data of the cerebral cortex

Curvilinear reformatting of three-dimensional (3D) MRI data of the cerebral cortex is a well-established tool which improves the display of the gyral structure, permits a precise localization of lesions, and helps to identify subtle abnormalities difficult to detect in planar slices due to the brain's complex convolutional pattern. However, the method is time consuming because it requires interactive manual delineation of the brain surface contour. Therefore, a novel technique for automatic curvilinear reformatting is presented. A T1-weighted MRI volume data set is normalized using SPM2. Due to the normalization to a common stereotactic space, predefined masks can be applied to cover skull and outer brain regions in different depths from the brain surface. Thereby, the outer brain regions are subsequently removed in 2-mm layers parallel to the brain surface like ‘peeling an onion’. The serial convex planes enclosing the residual inner part of the brain are presented 3-dimensionally. If necessary (e.g., for intraoperative navigation), the normalized data can be transferred to native space by inverse normalization. Compared to cross-sectional images, curvilinear reformatting offers a markedly superior visualization of topographic relations between lesions and cortical structures, helps to detect subtle cortical malformations and to assess the spatial extent of lesions, thus allowing a better planning of neurosurgical procedures. Compared to alternative methods, it is largely based on freely available software and does not require observer-dependent manual input. In conclusion, we present a simple, easy-to-use and fully automated method for curvilinear reformatting of 3D MRI.

Transforming Electrocortical Mapping Data into Standardized Common Space

Subdural grid electrodes are implanted routinely for the pre-surgical work up of epilepsy. While different approaches are available, many centers, including ours, visualize electrode locations by co-registering pre-operative 3-D MR images with post-implantation 3-D CT images. This method allows the determination of the electrode positions in relation to the individual patient's anatomy, but does not easily allow comparison across patients. The goal of this study was to develop and validate a method for transforming electrode positions derived from 3-D CT images into standardized space. We analyzed data from twelve patients with subdurally implanted electrodes. Volumetric CT and MRI images were co-registered and then normalized into common stereotactic space. Electrode locations were verified statistically by comparing distances between the anterior commissure and a representative sampling of 8 electrode sites per patient. Results confirm the accuracy of our co-registration method for comparing electrode locations across patients.

In vivo neuropathology of the hippocampal formation in AD: A radial mapping MR-based study

Early involvement of the hippocampal formation is the biological basis of the typical learning deficit in Alzheimer's disease (AD). However, the hippocampal formation is unevenly affected by AD pathology, deposits of plaques and tangles being particularly dense in the CA1 field and subiculum. The aim of the study was to locate in vivo the structural changes within the hippocampal formation in AD patients of mild to moderate severity. A group of 28 AD patients and 40 cognitively intact persons (age 74 ± 9 and 71 ± 7 years) underwent T1-weighted high-resolution MR scans. The hippocampal formation was isolated by manually tracing on 35 coronal slices the outlines of the hippocampus proper and subiculum after registration to a common stereotactic space. Group differences were assessed with algorithms developed ad hoc that make use of three-dimensional parametric surface mesh models. In AD patients, significant atrophic changes amounting to tissue loss of 20% or more were found in regions of the hippocampal formation corresponding to the CA1 field and part of the subiculum. Regions corresponding to the CA2–3 fields were remarkably spared. We conclude that the regions of the hippocampal formation that we found atrophic in AD patients are those known to be affected from pathological studies. This study supports the possibility of carrying out in vivo macroscopic neuropathology of the hippocampus with MR imaging in the neurodegenerative dementias.

The future appears to promise a more integrative approach to functional brain imaging.

This brain movie has the interesting property that any single image from it contains no information about brain function. Instead, information about brain function is encoded in the variance of image intensity over time. How then are such data typically analyzed to yield the now-familiar brain activation maps? The conventional approach to fMRI data analysis consists of three steps: preprocessing, regression, and inference [10]. In preprocessing, the raw images are subjected to spatial registration to correct for small head motions, temporally interpolated to compensate for the fact that different slices are acquired at different times, spatially smoothed to enhance signal to noise, and often spatially normalized or transformed into a common stereotactic space to facilitate group analyses and neuroanatomical labeling. In regression, the paradigm timing is convolved with an estimate of the hemodynamic impulse response function. The resultant hemodynamically lagged and blurred version of the paradigm timing is used as a regressor of interest, forming a general linear model, which is then fit to the data, allocating temporal variance in the (preprocessed) data among such regressors. In inference, the spatial map of regression coefficients resulting from the regression step is thresholded for significance, allowing formation of a map showing the suprathreshold regions as hot spots, often overlaid in color on a (higher resolution) anatomical MR image. This standard inferential univariate fMRI data analysis approach can be seen as an excellent machine for testing prior temporal hypotheses. However, it cannot discover unanticipated structure in the data, i.e., it cannot detect brain activations with timings that were unanticipated by the investigator. In the last decade, investigators have developed a variety of data-driven or exploratory techniques that can discover brain activity not anticipated in advance. It may be useful to view such approaches in the context of the finding [11] that in the resting state, synchronous fluctuations (or covariance) of voxel time courses were found throughout the bilateral motor cortex. Recent years have seen significant progress in paradigm design for fMRI as well as the development of other methods for assessing the functional anatomy of the human brain, such as diffusion tensor imaging [12] for mapping white matter fiber tracts. The future appears to promise a more integrative approach to functional brain imaging, in which data from multiple modalities are entered into comprehensive analyses of brain function and connectivity.

CNS & plasticity: sleep, juggling and pain

In neuroscience, next to „functional imaging„ some innovative new imaging techniques based on structural attributes have begun to be established and their potential recognized. Using the high spatial resolution of three-dimensional structural MRI-datasets, transformed into a common stereotactic space, morphometric techniques such as voxel-based (VBM) and deformation based analysis (VBM) are designed to seek significant regional differences by applying voxel-wise statistics in the context of Gaussian random fields. VBM is fully automated, unbiased, and has been cross-validated with region-of-interest measurements and functional data in a number of studies. VBM demonstrated in the past two years, that it is observer- independently capable of revealing subtle changes in grey matter volume/density by averaging across subjects. This technique establishes a 'lesion' in the brain that can not be detected by conventional MRI and may allow extremely subtle anatomical traits to be imaged and localised pointing the way to future neuropathological examination. In „idiopathic“ syndromes VBM has proven to be a powerful method to detect regional differences in cerebral structures in a variety of diseases like narcolepsy and restless legs syndrome, cluster headache and migraine, parkinsonian tremor, Huntington duisease and schizophrenia to name a few. Particularly for cluster headache it is remarkable, that findings in functional imaging and VBM have been directly translated into a successful therapeutical approach, i.e. deep brain stimualtion of the hypothalamus. Additionally, recent data regarding learning point towards the fundamental capability of the adult human cortex to adapt and change structurally in response to changes in the enviroment. This competence on a physiological level is crucial in our understanding of specific findings in so called idiopathic diseases. However, it is still one of the most interesting questions, whether those structural changes are primary or secondary to the syndrome. Only if we understand what exactly happens on a macroscopic and microscopic level, will we be in a position to use and translate our knowledge regarding plasticity into new treatment options. This will be extremely interesting with respect to progressive diseases such as dementia and chronic pain.

Comparison of functional activation foci in children and adults using a common stereotactic space

The development of methods allowing direct comparisons between child and adult neuroimaging data is an important prerequisite for studying the neural bases of cognitive development. Several issues arise when attempting to make such direct comparisons, including the comparability of anatomical localization of functional responses and the magnitude and time course of the hemodynamic responses themselves. Previous results suggest that, after transformation into a common stereotactic space, anatomical differences between children (ages 7 and 8) and adults are small relative to the resolution of fMRI data. Here, we investigate whether time courses (BOLD responses) and locations of functional activation foci show similarities as well. Event-related fMRI was performed on 16 children (ages 7 and 8) and 16 adults, who pressed buttons in response to a visual stimulus. After transforming images into Talairach space, the coordinates of four consistent activations in each hemisphere were determined for each subject: two foci in the sensorimotor cortex, one focus in the visual cortex, and one focus in the supplementary motor area (eight activations in total). In seven foci, time courses were similar between children and adults, and peak amplitudes of time courses were comparable in all eight foci. There were negligible between-group differences in location of all foci. Variability of activation location was statistically similar in the two groups. In voxelwise group comparison images, minimal differences were found between children and adults in visual and motor cortex regions. The small differences in time courses and locations of activation foci between child and adult brains validate the feasibility of direct statistical comparison of these groups within a common space.

Role of Operculoinsular Cortices in Human Pain Processing: Converging Evidence from PET, fMRI, Dipole Modeling, and Intracerebral Recordings of Evoked Potentials

Insular and SII cortices have been consistently shown by PET, fMRI, EPs, and MEG techniques to be activated bilaterally by a nociceptive stimulation. The aim of the present study was to refer to, and to compare within a common stereotactic space, the nociceptive responses obtained in humans by (i) PET, (ii) fMRI, (iii) dipole modeling of scalp LEPs, and (iv) intracerebral recordings of LEPs. PET, fMRI, and scalp LEPs were obtained from normal subjects during thermal pain. Operculoinsular LEPs were obtained from 13 patients using deep brain electrodes implanted for presurgical evaluation of drug-resistant epilepsy. Whatever the technique, we obtained responses which were located bilaterally in the insular and SII cortices. In electrophysiological responses (LEPs) the SII insular contribution peaked between 150 and 250 ms poststimulus and corresponded to the earliest portions of the whole cerebral response. Group analysis of PET and fMRI data showed highly consistent responses contralateral to stimulation. On single-subject analysis, LEPs and fMRI activations were concentrated in relatively restricted volumes even though spatial sampling was quite different for both techniques. Despite our multimodal approach, however, it was not possible to separate insular from SII activities. Individual variations in the anatomy and function of SII and insular cortices may explain this limitation. This multimodal study provides, however, cross-validated spatial and temporal information on the pain-related processes occurring in the operculoinsular region, which thus appears as a major site for the early cortical pain encoding in the human brain.

The Feasibility of a Common Stereotactic Space for Children and Adults in fMRI Studies of Development

Thequestion of whether pediatric and adult neuroimaging data can be analyzed in a common stereotactic space is a critical issue for developmental neuroscience. Two studies were performed to address this question. In Study 1, high-resolution structural MR brain images of 20 children (7–8 years of age) and 20 young adults (18–30 years of age) were transformed to a common space. Overall brain shape was assessed by tracing the outer boundaries of the brains in three orientations, and more local anatomy was assessed by analysis of portions of 10 selected sulci. Small, but consistent, differences in location and variability were observed in specific locations of the sulcal tracings and outer-boundary sections. In Study 2, a computer simulation was used to assess the extent to which the small anatomical differences observed in Study 1 would produce spurious effects in functional imaging data. Results indicate that, assuming a functional resolution of 5 mm in images averaged across subjects, anatomical differences in either variability or location between children and adults of the magnitude observed in Study 1 would not negatively affect functional image comparisons. We conclude that atlas-transformed brain morphology is relatively consistent between 7- and 8-year-old children and adults at a resolution appropriate to current functional imaging and that the small anatomical differences present do not limit the usefulness of comparing child and adult functional images within a common stereotactic space.

Neuroanatomical analysis of functional brain images: Validation with retinotopic mapping

AbstractThe analysis of functional brain images generated by positron emission tomography (PET) has depended on averaging individual images in a common stereotactic space to improve the signal‐to‐noise ratio in activation maps. Although the precise relationship of stereotactic coordinates to sulcul and gyral anatomy is obscured, these techniques have productively enabled exploratory, pixel‐based analysis of PET images. Coregistered three‐dimensional magnetic resonance (MR) datasets, not widely available at the time PET techniques were pioneered, now make it possible to develop complementary hypothesis‐led analysis techniques that respect individual anatomy and, therefore, allow conclusions in terms of sulcal and gyral anatomy. We report the development of such a technique, involving construction of a local standard space within anatomically‐defined boundaries. We validate the technique with a retinotopic mapping paradigm. In the analysis based on this standard space, regions of activation from the contributing subjects superimpose better than they do when Talairach's transformation is used. This approach also allows conclusions to be drawn specifically about striate cortex, whereas analysis of stereotactically transformed data does not distinguish V1 and V2. This approach is likely to be particularly useful for studying brain‐damaged subjects, to whom a universal stereotactic space cannot be applied. © 1995 Wiley‐Liss, Inc.